Helicobacter pylori γ-glutamyltranspeptidase upregulates COX-2 and EGF-related peptide expression in human gastric cells
Helicobacter pylori γ-glutamyltranspeptidase upregulates COX-2 and EGF-related peptide expression in human gastric cells
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DOI：
10.1046/j.1462-5822.2004.00366.x
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发表时间：
2004-03-01
影响因子：
3.4
通讯作者：
Zarrilli, R
中科院分区：
文献类型：
--
作者：
Busiello, I;Acquaviva, R;Zarrilli, R
幽门螺杆菌感染后胃黏膜细胞考克斯-2和EGF相关肽的表达增加我们试图研究在MKN 28和AGS胃粘膜细胞中参与考克斯-2、HB-EGF和双调蛋白上调的细菌毒力因子和宿主细胞途径。H.幽门螺杆菌菌株CCUG 17874在补充有0.2%（2，6-二甲基）-β-环糊精的布鲁氏菌肉汤中生长。通过排阻层析和阴离子交换层析对细菌在培养基中释放的可溶性蛋白进行了分离。得到保留上调考克斯-2和HB-EGF mRNA和蛋白质表达的能力的单峰。SDS-PAGE分析表明，该峰的两个肽具有38和22 kDa的表观分子量，通过自动Edman降解分析鉴定为H的N末端和C末端肽。pylori γ-谷氨酰转肽酶。选择性γ-谷氨酰转肽酶抑制剂Acivicin可抑制H. pylori诱导的考克斯-2和EGF相关肽mRNA表达上调。一个H。pylori同基因突变型γ-谷氨酰转肽酶缺陷株对考克斯-2、HB-EGF和双调蛋白mRNA表达无影响。阻断磷脂酰肌醇-3激酶和p38激酶，但不阻断MAP激酶激酶，抑制H。幽门螺杆菌γ-谷氨酰转肽酶诱导考克斯-2和EGF相关肽mRNA表达上调。
Gastric mucosa responds to Helicobacter pylori-induced cell damage by increasing the expression of COX-2 and EGF-related peptides. We sought to investigate the bacterial virulence factor/s and the host cellular pathways involved in the upregulation of COX-2, HB-EGF and amphiregulin in MKN 28 and AGS gastric mucosal cells. H. pylori strain CCUG 17874 was grown in Brucella broth supplemented with 0.2% (2,6-dimethyl)-beta-cyclodextrins. The soluble proteins released in the culture medium by the bacterium were fractionated by exclusion size and anion exchange chromatography. A single peak retaining the ability to upregulate COX-2 and HB-EGF mRNA and protein expression was obtained. SDS-PAGE analysis of the peak showed two peptides with an apparent molecular weight of 38 and 22 kDa, which were identified by automated Edman degradation analysis as the N-terminal and C-terminal peptides of H. pylori gamma-glutamyltranspeptidase respectively. Acivicin, a selective gamma-glutamyltranspeptidase inhibitor, counteracted H. pylori-induced upregulation of COX-2 and EGF-related peptide mRNA expression. An H. pylori isogenic mutant gamma-glutamyltranspeptidase-deficient strain did not exert any effect on COX-2, HB-EGF and amphiregulin mRNA expression. Blockade of phosphatidylinositol-3 kinase and p38 kinase, but not MAP kinase kinase, inhibited H. pylori gamma-glutamyltranspeptidase-induced upregulation of COX-2 and EGF-related peptide mRNA expression.